Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 16, Issue 15, Pages 7489-7493Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.06.005
Keywords
water transport; aquaporin; AQP4; antiepileptics; carbonic anhydrase
Funding
- National Institutes of Health [DK35124, EY13574, HL59198, EB00415, DK72517, HL73856]
- Cystic Fibrosis Foundation
Ask authors/readers for more resources
Inhibitors of brain glial water channel aquaporin-4 (AQP4) are of potential clinical utility, as they are predicted to modulate brain edema, neuroexcitation and glial scarring. Recently, Huber et al. (Bioorg. Med. Chem. 2007, 17, 1270-1273; in press) reported that a series of arylsulfonamides, antiepileptics, and related small molecules strongly inhibited AQP4 water transport with IC(50)s down to 1 mu M. We retested the compounds with greatest reported potencies, including acetylsulfanilamide, acetazolamide, 6-ethoxybenzothiazole-2- sulfonamide, topiramate, zonisamide, phenytoin, lamotrigine, and sumatriptan, in AQP4-transfected mammalian cells and primary cultures of brain glial cells, using several sensitive assays of osmotic water permeability. Contrary to the findings of Huber et al., in our studies we found no significant inhibition of AQP4 water permeability by any of the compounds at concentrations up to 100 mu M. (C) 2008 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available